Pharmacokinetics

Michaelis-Menten Kinetics

TRMichaelis-Menten Kinetiği
Also known as:Saturable kinetics · nonlinear elimination

A nonlinear pharmacokinetic model describing drug elimination that transitions from first-order at low concentrations to zero-order at high concentrations due to enzyme saturation.

Formula

Rate = Vmax × C / (Km + C) Dosing rate = Vmax × Css / (Km + Css) CL = Vmax / (Km + C)

In depth

Vmax is the maximum elimination rate and Km the concentration at which the rate is half of Vmax. When the concentration (C) is far below Km the rate approximates (Vmax/Km) × C; when C is far above Km it approaches Vmax. Apparent clearance therefore falls, and half-life lengthens, as concentration rises.

At steady state the dosing rate equals Vmax × Css / (Km + Css), so Css rises disproportionately as the dosing rate approaches Vmax, and the time to reach steady state also lengthens. Phenytoin is the classic clinical example, and its Vmax and Km vary widely between patients.

Clinical pearl

Phenytoin dose increments should be small and followed by repeat levels, because a modest increase near saturation can move a patient from subtherapeutic to toxic concentrations.

Example drugs

Phenytoin Ethanol Acetylsalicylic acid
TRIn Turkish

Michaelis-Menten Kinetiği

Düşük konsantrasyonlarda birinci derece, yüksek konsantrasyonlarda enzim doygunluğu nedeniyle sıfır dereceye geçiş yapan nonlinear ilaç eliminasyon modeli.

Vmax en yüksek eliminasyon hızı, Km ise hızın Vmax'ın yarısına eşit olduğu konsantrasyondur. Konsantrasyon (C) Km'nin çok altındayken hız yaklaşık (Vmax/Km) × C'dir; C, Km'nin çok üzerindeyken hız Vmax'a yaklaşır. Bu nedenle konsantrasyon arttıkça görünür klirens azalır ve yarılanma ömrü uzar.

Kararlı durumda doz hızı Vmax × Css / (Km + Css) değerine eşittir; dolayısıyla doz hızı Vmax'a yaklaştıkça Css orantısız biçimde yükselir ve kararlı duruma ulaşma süresi de uzar. Klasik klinik örnek fenitoindir; fenitoinin Vmax ve Km değerleri hastadan hastaya büyük farklılık gösterir.

Fenitoin dozu küçük adımlarla artırılmalı ve her artıştan sonra düzey yeniden ölçülmelidir; doygunluğa yakın düzeylerde küçük bir artış bile hastayı subterapötik düzeyden toksik düzeye taşıyabilir.

Diğer adları:Doyabilir kinetik · nonlinear eliminasyon
Updated 24.09.2026 22 views Educational reference — verify against current sources before clinical use.

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